Panahloo A, Mohamed-Ali V, Andrés C, Denver A E, Yudkin J S
Department of Medicine, University College London Medical School, Whittington Hospital, UK.
Metabolism. 1998 Jun;47(6):637-43. doi: 10.1016/s0026-0495(98)90023-3.
In non-insulin-dependent diabetes mellitus (NIDDM), cardiovascular risk factors improve during treatment, but whether insulin (I) differs from sulfonylurea (SU) therapy is unclear. To separate the contributions of improved diabetic control versus treatment regimen to risk factors, we examined the effects of SU and I on insulin sensitivity, basal and post-glucose load levels of insulin-like molecules, fibrinolysis, and lipid concentrations. Twenty poorly controlled, diet-treated NIDDM subjects were given I or SU each for a period of 16 weeks in a randomized crossover study, with a 4-week washout period between each treatment. Subjects were studied at the baselines (B1 and B2) and after each treatment. Treatment with I or SU produced similar improvements in glycemia (hemoglobin A1 [HbA1] B1, 11.7% +/- 2.1%; SU, 8.5% +/- 0.9%; I, 8.6% +/- 1.2%) and the metabolic clearance rate of glucose ([MCR-G] B1, 1.86 x/divided by 1.4; SU, 2.36 x/divided by 1.4 (P = .005 vB1); I, 2.27 x/divided by 1.4 (P = .07 vB1) ml x kg(-1) x min(-1)). On SU therapy, subjects had higher fasting and post-glucose load levels of intact proinsulin compared with B1 and I (fasting, 13.9 x/divided by 2.6 v 9.5 x/divided by 2.2 (P = .004) and 9.1 x/divided by 2.4 pmol x L(-1) (P = .01), respectively). Plasminogen activator inhibitor-1 (PAI-1) activity and antigen were higher than at B1 on SU therapy (23.7 v 19.9 AU x mL(-1) (P = .02) and 47.6 v 32.2 ng x mL(-1) (P = .006), respectively), but not on I. There were no changes compared with B1 and no differences between the two therapies in total, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) cholesterol and triglyceride, low-density lipoprotein (LDL), high-density lipoprotein 2 (HDL2) and HDL3 cholesterol, apolipoprotein (apo) A1, A2, and B1, or lipoprotein (a) [Lp(a)] levels. In conclusion, (1) treatment with SU or I resulted in equal improvement in glycemia and insulin sensitivity, (2) intact proinsulin and PAI-1 antigen and activity were higher on SU, and (3) there were no differences in lipid concentrations with improved glycemia or between therapies.
在非胰岛素依赖型糖尿病（NIDDM）中，心血管危险因素在治疗期间会有所改善，但胰岛素（I）治疗与磺脲类药物（SU）治疗是否存在差异尚不清楚。为了区分改善的糖尿病控制与治疗方案对危险因素的影响，我们研究了SU和I对胰岛素敏感性、胰岛素样分子的基础水平和葡萄糖负荷后水平、纤维蛋白溶解以及脂质浓度的影响。在一项随机交叉研究中，20名控制不佳、采用饮食治疗的NIDDM患者分别接受I或SU治疗，为期16周，每次治疗之间有4周的洗脱期。在基线（B1和B2）以及每次治疗后对患者进行研究。I或SU治疗在血糖控制方面产生了相似的改善（糖化血红蛋白A1[HbA1]：B1时为11.7%±2.1%；SU治疗后为8.5%±0.9%；I治疗后为8.6%±1.2%）以及葡萄糖的代谢清除率（[MCR-G]：B1时为1.86×/除以1.4；SU治疗后为2.36×/除以1.4（与B1相比P = 0.005）；I治疗后为2.27×/除以1.4（与B1相比P = 0.07）ml·kg⁻¹·min⁻¹）。在SU治疗时，与B1和I治疗相比，患者的完整胰岛素原空腹水平和葡萄糖负荷后水平更高（空腹时分别为13.9×/除以2.6对9.5×/除以2.2（P = 0.004）和9.1×/除以2.4 pmol·L⁻¹（P = 0.01））。在SU治疗时，纤溶酶原激活物抑制剂-1（PAI-1）的活性和抗原水平高于B1时（分别为23.7对19.9 AU·mL⁻¹（P = 0.02）和47.6对32.2 ng·mL⁻¹（P = 0.006）），但I治疗时无此变化。与B1相比，总胆固醇、极低密度脂蛋白（VLDL）、中间密度脂蛋白（IDL）胆固醇和甘油三酯、低密度脂蛋白（LDL）、高密度脂蛋白2（HDL2）和HDL3胆固醇、载脂蛋白（apo）A1、A2和B1或脂蛋白（a）[Lp（a）]水平在两种治疗之间均无变化，且两种治疗之间无差异。总之，（1）SU或I治疗在血糖和胰岛素敏感性改善方面效果相同；（2）SU治疗时完整胰岛素原以及PAI-1抗原和活性更高；（3）血糖改善时脂质浓度在两种治疗之间无差异。
